Our overarching goal is to define the neural substrates of taste and flavor in humans. This application is for a project that will use functional magnetic resonance imaging (fMRI) to measure brain response in healthy human volunteer subjects to tastes presented in isolation and tastes presented with odors. The neural substrates of taste must code for three major perceptual dimensions of taste; namely, intensity, affect, and quality. Previous studies comparing pleasant to unpleasant taste have not equated stimuli for intensity and no study has measured brain response to the different concentrations of the same taste. Our first specific aim is to determine brain regions coding for taste intensity versus taste pleasantness/unpleasantness. We will present subjects with two concentrations each of a pleasant and unpleasant taste while their brain response is measured with fMRI. Analyses will then be performed to isolate the brain response to intensity regardless of affective valence and affect regardless of intensity. Our second aim is to use fMRI to investigate brain correlates of simultaneous presentation of taste and smell versus independent presentation with either a taste or a smell. Congruent (vanilla odor with sweet taste) and incongruent (vanilla odor with salty taste) taste/smell pairs will be presented to investigate the effect of experience on integration. Additionally, mode of odor presentation (orthonasal versus retronasal delivery) will also be investigated. When taste and smell co-occur naturally the odor is perceived via the retronasal route. We thus predict differential integration of odor with taste favoring the retronasal route. Understanding the neural correlates of taste and flavor offers a mechanism by which limbic system function can be probed in health and disease. For example, the response function of the fMRI signal to taste concentration may be used as an objective probe for limbic system response in an analogous way that the flickering checkerboard has been used to define the characteristics of the fMRI signal in the visual cortex. Furthermore, imaging studies of taste intensity response may also be used to demonstrate the integrity of limbic system function in patient populations with suspected limbic system involvement (e.g., Alzheimer's disease) or patients who may respond abnormally to food stimuli (e.g., bulimia). This research will also provide important information into the nature of polymodal sensory integration. [unreadable] [unreadable]